We propose to develop a new platform for identifying key B cell epitope mimetics in the form of synthetic peptides, called peptoids. We will demonstrate that they can be used to generate antibodies against the native protein. Housed on microarrays, these peptoids will be screened with sera containing known antibodies. The peptoids that bind to native-protein-reactive antibodies will be linked to conventional carrier proteins and injected in adjuvant to induce immunity. By systematically studying a well-defined system of a polyclonal antibody and a protein antigen, each variable and parameter will be tested and optimized. Specific Aims: 1) To optimize parameters for screening peptoid libraries with well-defined antibodies and to demonstrate that the antibodies that are reactive with these peptoids also bind to the native antigen. 2) Using the screening parameters determined in Aim 1, to develop a subtraction-based screen to detect peptoids that bind to one panel of antibodies and not to another and to again prove that these antibodies are reactive to the corresponding native antigen. Additionally, we will use this screen to identify consensus peptoid hits, those bound by both panels of antibodies. 3) To determine whether the peptoids from the subtraction screen developed in Aim 2, attached to carrier proteins and administered in adjuvant, act as highly immunogenic B cell epitope mimetics. If our experiments are successful in this model system, this platform will be applicable to the development of much-needed vaccines against a wide variety of pathogens and toxins, particularly those where mutation of antigens and the development of drug resistance are problematic. PUBLIC HEALTH RELEVANCE: Our goal is to develop a new platform to generate safe and effective peptoid vaccines against a variety of pathogens. The objective of this proposal is to test this concept in a well defined model system.